Details

Autor(en) / Beteiligte

• Dickinson, Robin J
• Keyse, Stephen M

Titel

Diverse physiological functions for dual-specificity MAP kinase phosphatases

Ist Teil von

• Journal of cell science, 2006-11, Vol.119 (22), p.4607-4615

Ort / Verlag

England: The Company of Biologists Limited

Erscheinungsjahr

2006

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• A structurally distinct subfamily of ten dual-specificity (Thr/Tyr) protein phosphatases is responsible for the regulated dephosphorylation and inactivation of mitogen-activated protein kinase (MAPK) family members in mammals. These MAPK phosphatases (MKPs) interact specifically with their substrates through a modular kinase-interaction motif (KIM) located within the N-terminal non-catalytic domain of the protein. In addition, MAPK binding is often accompanied by enzymatic activation of the C-terminal catalytic domain, thus ensuring specificity of action. Despite our knowledge of the biochemical and structural basis for the catalytic mechanism of the MKPs, we know much less about their regulation and physiological functions in mammalian cells and tissues. However, recent studies employing a range of model systems have begun to reveal essential non-redundant roles for the MKPs in determining the outcome of MAPK signalling in a variety of physiological contexts. These include development, immune system function, metabolic homeostasis and the regulation of cellular stress responses. Interestingly, these functions may reflect both restricted subcellular MKP activity and changes in the levels of signalling through multiple MAPK pathways.